The goals of the project are to study the glial gene expression of growth factors, myelin-related proteins and other glial proteins during nervous system injury and regeneration. In cuprizone intoxication and experimental autoimmune encephalomyelitis, there is demyelination, relative preservation of axons and myelin regeneration during clinical recovery. When focal cryogenic lesions are produced in dorsal columns of rat thoracic spinal cords, axons and myelin sheaths degenerate; glial cells and vessels survive and there is no hemorrhage or cavitation. During recovery, axons regrow and become remyelinated by Schwann cells and oligodendrocytes. Our recent studies have shown that in all three types of myelin injury associated with regeneration, hypertrophic reactive astrocytes in the lesions express the mRNAs and peptides for IGF-I and its binding protein IGFBP-2. As recovery and remyelination begin, the IGF-I receptor is expressed by oligodendroglia, the cells responsible for myelin regeneration. To test whether injury restricted to neurons produced the same astrocytic response, we examined astrocytic gene expression of GFAP and IGF-related proteins during retrograde degeneration of motor neurons following facial nerve transection. Compared to demyelination-induced astrocytic responses, neuronal injury induced less elevation of IGF-related protein gene expression by astrocytes. Finally, similar tests of IGF expression were carried out on rats with experimental autoimmune neuritis. This peripheral nerve disease produces brisk microglial cell activation in the spinal cord without inflammation or other cellular abnormalities. Although astrocytic expression of glial fibrillary acidic protein was increased, no increases in expression of IGF-I or IGFBP-2 were detected. This suggests that microglial cell activation alone does not have a major role in the induction of IGF-I gene expression during CNS injury.